Saliva is a complex body fluid containing many proteins of both glandular and nonglandular origin. The nature and function of salivary proteins in oral physiology have to be more fully understood and defined in biochemical terms if one is to adequately understand the events which lead to pellicle and plaque formation. Studies in our laboratory resulted in the isolation and partial characterization of a group of proline-rich proteins from human parotid saliva. These highly soluble proteins are of special interest because they exhibit a high affinity for hydroxyapatite, contain phosphate, show genetic polymorphism and display in many respects fascinating similarities to structural proteins such as collagen and enamel protein. It is, therefore, our aim to elucidate the chemical characteristics of these unusual proteins. In this endeavour we will investigate a) the primary structure of all four proline-rich proteins, b) their relationship to collagen and related proteins using proteolytic enzymes such as collagenases, c) their secondary and tertiary structure by circular dichroism, d) the genetic polymorphism on a molecular level and e) the biosynthesis and fate of these proteins upon their release into the oral cavity. Insofar as possible antisera against these proteins will be used to locate their biosynthetic pathway in tissue culture systems and to quantitate their content in oral fluids in both normal and diseased subjects. Our overall objective is, therefore, to fully understand the chemistry and structure of this unique group of proteins, which will enable us to conduct comparative studies with proteins of the connective tissue class and facilitate the elucidation of their role in nature and certain oral diseases.